Discovering Our Roots: The Origins of the Human Genome Project
By Rachel Lines, Behavioral Neuroscience, 2023
Humans share a DNA code that is 99.9 percent identical among all individuals. Encoding physical traits, instructing development, and containing information about probability of disease, DNA tells the story of humanity’s past, and individuals’ connections to one another. In order to advance the understanding of the human genome, which is the complete compilation of human genes derived from over three million DNA base pairs, the Human Genome Project began to analyze the human recipe in 1988.
Robert Sinsheimer was one of the first individuals to realize the potential of sequencing the human genome. Walter Gilbert, who developed the technique for genetic sequencing, enlisted the help of James Watson, a scientist famous for discovering the double helical structure of DNA. Originally, the strategy to understand the genome involved utilization of bacterial artificial chromosomes, which contain fragments of human DNA. To identify disease-related genes, scientists performed sequencing that utilized clones of these artificial chromosomes. As the project evolved, the Celera approach emerged, thus sequencing the whole genome through the cloning of random chromosomal fragments. Finally, technological development allowed sequencing to rely on algorithms and computer processing.
Although the idea was fascinating, many people doubted the scientific merits of the Human Genome Project. The estimated price of the project was a daunting three billion dollars. Additionally, the majority of DNA does not actually code for genes — so, was it worth the cost to map the entire genome? Consequently, scientists used model organisms to reduce the price tag. Sequencing simpler organisms enabled researchers to observe a preview of the human genome.
DNA tells the story of humanity’s past, and individuals’ connections to one another.
Although knowledge of the human genome provided many medical benefits, issues arose due to consequences of privacy, consent, and genetic testing. The Ethical, Legal, and Social Implications (ELSI) Program played an essential role in preventing conflicts. Individual privacy and fairness were carefully protected, especially considering the use of individuals’ genetic information. Informed consent was also essential, as humans were the genetic research subjects. Furthermore, knowledge of the human genome became increasingly controversial because of the developing potential for genetic testing of embryos during pregnancy.
In April 2003, the International Human Genome Sequencing Consortium released a high-quality sequence of the human genome. Through the use of model organisms, researchers also sequenced the mouse genome, and the genomes of several other organisms. The development of this sequence resulted in the formation of techniques which currently allow for the study of thousands of genes at one time.
Knowledge of the human genome allows for better understanding of familial disease, genetic disorders, and even susceptibility to addiction. The Chesler Lab within the Jackson Laboratory in Bar Harbor, Maine is a prime example of a team currently working on advancing knowledge of the human genome. In this lab, experts use mouse models to analyze impulsivity, response to novelty, and drug abuse.
Chesler explained, ‘“some people argue that you cannot tell whether or not a mouse is depressed; you can’t ask it how it feels.”
Initially, the mice used at the Jackson Laboratory began as a collection of cute, pet mice. The founder of Jackson Labs, Clarence Cook, studied whether the traits in these fancy mice were heritable. Using systematic crossing of inbred mice, the laboratory developed mouse variants bred for specific traits and lineages. Through definition of the mice genomes, the sequence data was able to be correlated with complex traits.
Humans and mice share around 95 percent of their genes, meaning research on the mouse genome can be compared to human research. A 2016 study performed by the Jackson Laboratory revealed genes related to cocaine sensitization, and suggested mechanisms that drive human cocaine use. Elissa Chesler, the principle investigator at the Chesler Lab, explained that studies such as these can help define what good recovery from drug use looks like, and how to replicate it. Additionally, she said it can be controversial to study mental illness in mouse populations. In an interview, Chesler explained, ‘“some people argue that you cannot tell whether or not a mouse is depressed; you can’t ask it how it feels.”’ However, these mice can be genetically modified to express the biological aspects of depression similar to those of humans, and can then be studied. New research includes the study of vulnerability to drug abuse, and the study of biological changes resulting from addiction.
The Jackson Laboratory is only one example of researchers working towards an improved understanding of genomics. Although the Human Genome Project ended in 2003, the knowledge and understanding of the human genome continues to evolve.
Nature (2018). DOI: 10.1038/d41586–018–05462-w
Science (2001). DOI: 10.1126/science.291.5507.1218
Psychopharmacology (2016). DOI: 10.1007/s00213–015–4147-z
